- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05174559
Additional Dietary Large Neutral Amino Acids (LNAA) for Improved Symptoms in Adult Classical Phenylktonuria (PKU)
November 30, 2023 updated by: Shoji Yano, University of Southern California
Can Care of Adult PKU Be Improved With Additional Dietary Large Neutral Amino Acids: An N-of-1 Study
This research investigates the effects of combining a phenylalanine restricted diet (usual care) with LNAA supplementation (adjuvant LNAA) in well-controlled adults with classical PKU.
The hypothesis is that symptoms are improved in well-controlled patients who receive adjuvant LNAA therapy compared with diet monotherapy.
Six symptomatic classical PKU adults will be enrolled to test the hypothesis in a small series of N-of-1 randomized controlled trials over 18-weeks.
All assessments will be collected in patient's homes.
A 3-month follow-up period will assess the longer-term effects of adjuvant LNAA in patients who show clinical benefit at the end of the intervention period.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
Clinical care of PKU confronts an increasing proportion of early-treated well-controlled adults, with a treatment goal that quality of life be as normal as possible.
Even adults who have successfully managed their blood phenylalanine levels from birth can have symptoms which impact daily function.
New therapies that target symptoms are needed, especially for symptomatic well-controlled classical adults with few treatment options.
In Denmark and the LAC+USC U.S. clinic, adults are offered large neutral amino acid (LNAA) supplements when diet monotherapy becomes less effective for symptom management, or the patient wants a less restrictive diet.
Many patients report improved symptoms.
LNAA supplementation doesn't significantly reduce blood phenylalanine, suggesting a different mechanism for patient perceived benefits.
Both LNAA supplementation and a phenylalanine restricted diet aim to improve brain neurotransmitter biochemistry to optimize outcomes through dietary intervention.
The overall objective of this research is to evaluate additional dietary LNAAs on symptom management in adults with classical PKU at an individual level.
N-of-1 randomized controlled trials will provide the highest level of evidence.
The scientific premise is that manipulation of dietary LNAAs affects blood LNAA concentrations.
LNAAs compete with phenylalanine for a shared transporter from blood to brain, dependent on blood concentrations and transporter affinities.
Higher blood phenylalanine levels in adult PKU, with high transport affinity, produces excessive phenylalanine brain entry at the expense of other LNAAs.
Insufficient LNAAs impairs synthesis of chemicals in the brain (neurotransmitters), a suggested mechanism of action for adult PKU symptoms.
Additional dietary LNAAs may help to overcome this limitation of adult usual care.
The study uses established PKU treatment products (medical foods) and biomarkers, (1) to determine effect of the adjuvant LNAA diet in symptom management; and (2) to evaluate correlations between changes in biomarkers and changes in symptoms during the intervention.
Should findings show additive clinical value of LNAAs to the PKU diet, the strategy may become a useful adjunct.
For participants, results will bring them closer to evidence-based individualized care.
This work could advance the field closer toward personalized management.
Study Type
Interventional
Enrollment (Estimated)
10
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Kathryn Moseley, RD, MS
- Phone Number: 714-642-8790
- Email: kmoseley@usc.edu
Study Contact Backup
- Name: Annie Prince, RD. PhD
- Phone Number: 9713733482
- Email: ap_867@usc.edu
Study Locations
-
-
California
-
Los Angeles, California, United States, 90033
- University of Southern California
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- age ≥ 18 years
- diagnosis of classical PKU (blood phenylalanine ≥1200 µmol pre-treatment or off-treatment
- ≥ 2 PKU-related symptoms with clinically meaningful negative impact on daily life
- is in regular clinical monitoring and is treated with a PKU diet with a natural protein restriction and medical foods
- average blood phenylalanine levels between 360 and 900 µmol in past one year
- able and willing to provide consent
- demonstrates capacity to complete all requirements of the protocol
- if on medications approved by the Principal Investigator agrees not to alter dose for duration of study
- has stable daily access to phone, internet, and physical address
Exclusion Criteria:
- women who are breastfeeding, pregnant or planning to become pregnant in the next year
- use of adjuvant PKU treatments (LNAAs, Kuvan®, Palinziq®) within past 3 months
- use of psychotropic medications, melatonin, or any serotonin-reuptake inhibitors within past 3 months
- demonstrates insufficient motivation or time required to complete full trial
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active LNAA
Active LNAA tablets are given to each participant in 3 multiple crossovers for a total exposure to the Active Comparator 3 times.
The allocation is randomized within each cycle of two treatments (active/inactive).
There are 3 total cycles for each participant.
The intervention is PreKUnil® tablets.
|
PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.
PreKUnil® inactive LNAA is a customized placebo for this research.
|
Placebo Comparator: Inactive LNAA
Inactive LNAA tablets (placebos) are given to each participant in 3 multiple crossovers for a total exposure to the Inactive Comparator 3 times.
The allocation is randomized within each cycle of two treatments (inactive/active).
There are 3 total cycles for each participant.
The placebo intervention is PreKUnil® placebo tablets.
|
PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.
PreKUnil® inactive LNAA is a customized placebo for this research.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Personalized Symptom Index
Time Frame: 3 weeks
|
Assesses the subjective effect of the interventions on the personally relevant two most bothersome symptoms for the individual patient as identified in a Symptom Elicitation Interview
|
3 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute plasma phenylalanine concentration, dried blood spots (finger-prick method)
Time Frame: 3 weeks
|
Primary FDA-qualified biomarker for PKU
|
3 weeks
|
Fasting plasma LNAAs, dried blood spots (finger-prick method)
Time Frame: 3 weeks
|
Secondary biomarkers such as the plasma Phe/Tyr ratio, Tyr/LNAA, Trp/LNAA ratio
|
3 weeks
|
Urine peripheral biomarkers of neurotransmitters, dried urine spots
Time Frame: 3 weeks
|
6-sufatoxymelatonin and dopamine
|
3 weeks
|
Computerized neuropsychological testing (responses over study iPad from home)
Time Frame: 3 weeks
|
Cambridge Neuropsychological Test Automated Assessment Battery (CANTAB) customized for study
|
3 weeks
|
PKU-QOL Questionnaire Adult version (responses over study iPad from home)
Time Frame: 3 weeks
|
65-item (20 min) Patient-Reported Outcome Measure of the impact of PKU and the PKU diet on quality of life
|
3 weeks
|
Psychological General Well-Being Index (responses over study iPad from home)
Time Frame: 3 weeks
|
22-item (15 min) Patient-Reported Outcome Measure of well-being
|
3 weeks
|
Adult ADHD Self-Report Scale (ASRS v1.1)
Time Frame: 3 weeks
|
9-item inattention subscale (10 min) Patient-Reported Outcome Measure of attention
|
3 weeks
|
3-Day Diet Record
Time Frame: 3 weeks
|
Complete recording of 24-hr intake for 3 days (45 min)
|
3 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Shoji Yano, MD, PhD, Keck School of Medicine at USC
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 1, 2023
Primary Completion (Estimated)
July 31, 2024
Study Completion (Estimated)
July 31, 2024
Study Registration Dates
First Submitted
December 13, 2021
First Submitted That Met QC Criteria
December 13, 2021
First Posted (Actual)
December 30, 2021
Study Record Updates
Last Update Posted (Estimated)
December 4, 2023
Last Update Submitted That Met QC Criteria
November 30, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- LNAA for PKU
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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